Details

Autor(en) / Beteiligte

• P Merke, Deborah
• Mallappa, Ashwini
• Arlt, Wiebke
• de La Perriere, Aude Brac
• Hirschberg, Angelica Lindén
• Juul, Anders
• Newell-Price, John D. C.
• G Perry, Colin
• Prete, Alessandro
• Rees, Aled
• Reisch, Nicole
• Stikkelbroeck, Nike
• Tourraine, Phillippe
• Maltby, Kerry
• Treasure, F Peter
• Porter, John
• Ross, Richard J

Titel

Modified-release Hydrocortisone in Congenital Adrenal Hyperplasia

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2021-02

Ort / Verlag

Endocrine Society

Erscheinungsjahr

2021

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• BackgroundStandard glucocorticoid therapy in congenital adrenal hyperplasia regularly fails to control androgen excess, causing glucocorticoid over-exposure and poor health outcomes. We investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control.Methods6-month randomized phase III study, MR-HC versus standard glucocorticoid, followed by single-arm MR-HC extension study. Primary outcomes were change in 24-hour standard deviation score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase III, and efficacy, safety and tolerability of MR-HC for the extension study.ResultsThe phase III study recruited 122 adult CAH patients. While the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P=0.007) and 12 (P=0.019) weeks, and between 07:00h to 15:00h (P=0.044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (<1200 ng/dl) was 52% at baseline, at 6 months 91% for MR-HC and 71% for standard therapy (P=0.002), and 80% for MR-HC at 18 months extension. The median daily hydrocortisone dose was 25mg at baseline, at 6 months 31mg for standard therapy and 30mg for MR-HC, and after 18 months 20mg MR-HC. Three adrenal crises occurred in phase III, none on MR-HC and 4 in extension study. MR-HC resulted in patient-reported benefit including menses restoration in eight patients (one on standard therapy), and 3 patient and 4 partner pregnancies (none on standard therapy).ConclusionMR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit.